Antimalarial drugs appear safe in early pregnancy

That’s the finding of the largest ever study to assess the effects of malaria and its treatment in the first trimester of pregnancy.

The malaria parasite is transmitted by mosquitos.

Despite the risks of malaria for pregnant women, there is very little published evidence on the effects of malaria and taking antimalarial drugs during the first trimester of pregnancy.

This is in part because antenatal clinic services are often unavailable in the rural tropics, and also because pregnant women are usually excluded from clinical trials of new drugs due to the risks of side-effects. No randomised controlled trial has ever been carried out on how best to treat malaria in the first trimester.

‘Malaria is a potentially deadly disease and is particularly dangerous during pregnancy, both to the health of the mother and to the health of her unborn child. Understanding the risks is essential for weighing up the treatment options,’ explains Dr Rose McGready, a Reader in Tropical Medicine at Oxford University, who led the work.

The study led by Oxford University researchers at the Shoklo Malaria Research Unit (SMRU) in Thailand, and funded by the Wellcome Trust, is published in the journal Lancet Infectious Diseases.

Malaria is particularly dangerous during pregnancy. Understanding the risks is essential for weighing up the treatment options.

Dr Rose McGready

The researchers examined medical records of women attending the unit’s antenatal clinic over the 25 years since it was founded. The outcomes for 16 668 women who did not contract malaria during pregnancy were compared with 945 women who had a single episode of malaria in the first trimester of their pregnancy.

The researchers found that malaria increased the risks of miscarriage from one in five pregnancies (in women without malaria) to one in two pregnancies.

Where women were infected with malaria but had no noticeable symptoms (asymptomatic malaria), the risk of miscarriage was one in three pregnancies.

Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization as the treatment for all malaria caused by the P. falciparum species of malaria parasite – except in the first trimester of pregnancy. This is because animal studies have indicated that the drugs can be toxic to embryos.

Yet the researchers found that after first-trimester malaria treatment, the likelihood of miscarriage was similar in women treated with chloroquine (26%), quinine (27%), and artemisinin (31%). And there were no differences between the treatments in other outcomes such as stillbirth or low birth weight.

‘Our work has highlighted the particular risk factors with malaria infection during pregnancy,’ says Dr McGready. ‘Particularly worrying is the risk of miscarriage even when the disease is asymptomatic. However, while the dangers of miscarriage are considerable, our study offers some good news – that the most common drugs reduce this risk significantly.’

The researchers conclude: ‘A randomised trial of first-trimester artemisinin-based treatment is now needed to make firm recommendations on the safety of first-trimester malaria treatments with this class of antimalarial drug.’

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